Neurons in cell cultures directly exposed to tetanus toxin undergo a period of increased excitation followed by a loss of spontaneous and evoked synaptic activity. The time to onset of the convulsant action of the toxin is dependent on toxin concentration. Morphologic techniques are being used in an attempt to correlate toxin localization with the characteristic stages of toxin action. Radioisotope studies indicate that the toxin is degraded in cultures with a half-life of approximately six days. Light microscope radioautography demonstrates that the toxin is preferentially associated with neurons and its neuronal distribution does not change up to two weeks after toxin removal from the culture medium. The synaptic ultrastructure of electrically quiet neurons is not obviously altered. Preliminary studies with toxin-colloidal gold complexes indicate that the toxin is internalized into neuronal somata and into synaptic varicosities.